Summary

Cognitive impairments in schizophrenia are the most debilitating aspect of the illness and
poorly treated by current medications. This study investigates transcranial direct current
stimulation (tDCS) - a safe, noninvasive weak electrical current delivery to stimulate brain
function - as a novel therapeutic for cognition in schizophrenia. Integrating
neurostimulation, electrophysiology and neuroimaging, this project aims to study tDCS
effects on cognition by verifying therapeutic target engagement, evaluating the tolerability
of tDCS sessions, and optimizing treatment parameters.

Description

Cognitive deficits are a strong predictor of functional outcome in schizophrenia, yet poorly
remediated by current treatments. Disturbances in dorsolateral prefrontal cortex (DLPFC)
function underlie core impairments such as in cognitive control and thus represent a
critical target for novel therapeutics. Initial studies indicate transcranial direct-current
stimulation (tDCS) may be effective in reducing symptoms due to DLPFC dysfunction. While
tDCS potentially represents an exciting, novel therapeutic advance, a number of basic
questions should be addressed prior to conducting larger-scale clinical trials, including:
verifying therapeutic target engagement, optimizing treatment parameters, and evaluating for
meaningful clinical effects. Recent studies employing tDCS to enhance prefrontal cortical
function in schizophrenia applied stimulating electrodes over the left frontal scalp region,
putatively targeting the left DLPFC. However, explicit confirmation of such target
engagement is lacking. Further, EEG studies have demonstrated close links of frontal
cortical gamma oscillations to cognitive control processes but modulation of this critical
physiologic process has not been investigated. Accordingly, the primary aim of this study is
to employ multimodal imaging to explicitly test for the assumed DLPFC engagement (fMRI) and
modulation of frontal gamma activity (EEG) by tDCS. This study will also investigate the
optimization of tDCS application parameters. Analogous to dose-finding investigations in
drug studies, we will conduct a parametric investigation of optimal current strengths. Also,
while there is extensive evidence for tolerability of single session tDCS, confirmation of
feasibility of multisession optimized protocols in schizophrenia is lacking and so will be
explicitly evaluated.

In summary, a successful outcome of this study would provide tDCS the sound mechanistic and
methodologic basis for more definitive testing in large-scale clinical trials as a highly
innovative therapeutic intervention for cognitive impairments in schizophrenia.

Recently, techniques to non-invasively modulate specific brain areas gained popularity in the form of transcranial direct current stimulation (tDCS) and high-definition transcranial direct current sti...

Semantic processing allows us to use conceptual knowledge about the world. It has been associated with a large distributed neural network that includes the frontal, temporal and parietal cortices. Rec...

Medical and Biotech [MESH] Definitions

Evoked Potentials, Motor

The electrical response evoked in a muscle or motor nerve by electrical or magnetic stimulation. Common methods of stimulation are by transcranial electrical and TRANSCRANIAL MAGNETIC STIMULATION. It is often used for monitoring during neurosurgery.

Electric Stimulation Therapy

Application of electric current in treatment without the generation of perceptible heat. It includes electric stimulation of nerves or muscles, passage of current into the body, or use of interrupted current of low intensity to raise the threshold of the skin to pain.

Catheter Ablation

Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DC-shock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias.

Electric Impedance

The resistance to the flow of either alternating or direct electrical current.

Electrical Synapses

Specialized junctions between NEURONS which connect the cytoplasm of one neuron to another allowing direct passage of an ion current.

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